Diastolic and systolic left ventricular dysfunction and mortality in chronic kidney disease patients on haemodialysis.

AIMS: Left ventricular diastolic dysfunction (LVDD) and LV systolic dysfunction (LVSD) are prevalent in CKD, but their prognostic relevance is debatable. We intent to verify whether LVDD and LVSD are independently predictive of all-cause mortality and if they have comparable or different effects on outcomes. METHODS: A retrospective analysis was conducted of the echocardiographic data of 1285 haemodialysis patients followed up until death or transplantation. LVDD was classified into 4 grades of severity. Endpoint was all-cause mortality. RESULTS: During a follow-up of 30 months, 419/1285 (33%) patients died, 224 (53%) due to CV events. LVDD occurred in 75% of patients, grade 1 DD was the prevalent diastolic abnormality, and pseudonormal pattern was the predominant form of moderate-severe DD. Moderate-severe LVDD (HR 1.379, CI% 1.074-1.770) and LVSD (HR 1.814, CI% 1.265-2.576) independently predicted death; a graded, progressive association was found between LVDD categories and the risk of death; and the impact of isolated severe-moderate LVDD on the risk of death was comparable to that exercised by isolated compromised LV systolic function. CONCLUSION: Moderate-severe LVDD and LVSD were independently associated with a higher probability of death and had a similar impact on survival. A progressive association was observed between LVDD grades and mortality.

Early cardiovascular events and cardiovascular death after renal transplantation: role of pretransplant risk factors.

BACKGROUND: The purpose of this study was to verify the risk factors present in patients on the kidney transplant waiting list that may interfere with the incidence of cardiovascular (CV) events and death during the first 12 months after transplantation. METHODS: Based on the data collected prospectively during pretransplant workups, a retrospective study was conducted including 665 patients followed up until death or completing 12 months posttransplantation. Endpoints were the composite incidence of CV events and death. RESULTS: The prevalence of diabetes, LV hypertrophy, and CV disease at baseline was high; 14% of patients had angina, 26% an abnormal myocardial scan, and 47% coronary artery disease. CV events occurred in 53 patients (8.4%) and in 29 (55%) caused death. The independent predictors of events were age ≥ 50 years (HR 2.292; CI% 1.093-4.806), angina (HR 1.969; CI% 1.039-3.732), and altered myocardial scan (HR 1.905, CI% 1.059-3.428). Altered myocardial scan (HR 2.822, 95% CI 1.095-6.660) was also one of the independent predictor of CV death. CONCLUSION: The incidence of CV events and death were predicted by variables associated with myocardial ischemia, a potentially modifiable risk factor. Patients with pretransplantation myocardial ischemia should be considered at a higher risk of developing early CV complications and managed accordingly before, during, and after kidney transplantation.

The Role of the Heart Team in Patients with Diffuse Coronary Artery Disease Undergoing Coronary Artery Bypass Grafting.

BACKGROUND: In patients eligible for coronary artery bypass grafting, no data assess the importance of the Heart Team in programming the best surgical strategy for patients with diffuse coronary artery disease (CAD). This study aims to determine the contribution of the Heart Team in predicting the feasibility of coronary artery bypass graft and angiographic surgical success in these patients based on visual angiographic analysis. METHODS: Patients with diffuse and severe CAD undergoing incomplete coronary artery bypass graft surgery were prospectively included. One-year postoperative coronary angiograms were obtained to evaluate graft occlusion. Two clinical cardiologists, two cardiovascular surgeons, and one interventional cardiologist retrospectively analyzed preoperative angiograms. A subjective scale was applied at a single moment to quantify the chance of successful coronary artery bypass grafting for each coronary territory with anatomical indication for revascularization. Based on individual scores, the Heart Team's and the specialists' scores were calculated and compared. RESULTS: The examiners evaluated 154 coronary territories, of which 85 (55.2%) were protected. The Heart Team's accuracy for predicting the angiographic success of the surgery was 74.9%, almost equal to that of the surgeons alone (73.2%). Only the interventional cardiologist predicted left anterior descending territory grafting success. The Heart Team had good specificity and reasonable sensitivity, and the surgeons had high sensitivity and low specificity in predicting angiographic success. CONCLUSION: The multispecialty Heart Team achieved good accuracy in predicting the angiographic coronary artery bypass graft success in patients with diffuse CAD, with a high specificity and reasonable sensitivity.

Postprandial increase in glucagon-like peptide-1 is blunted in severe heart failure.

The relationship between disturbances in glucose homeostasis and heart failure (HF) progression is bidirectional. However, the mechanisms by which HF intrinsically impairs glucose homeostasis remain unknown. The present study tested the hypothesis that the bioavailability of intact glucagon-like peptide-1 (GLP-1) is affected in HF, possibly contributing to disturbed glucose homeostasis. Serum concentrations of total and intact GLP-1 and insulin were measured after an overnight fast and 15 min after the ingestion of a mixed breakfast meal in 49 non-diabetic patients with severe HF and 40 healthy control subjects. Similarly, fasting and postprandial serum concentrations of these hormones were determined in sham-operated rats, and rats with HF treated with an inhibitor of the GLP-1-degrading enzyme dipeptidyl peptidase-4 (DPP4), vildagliptin, or vehicle for 4 weeks. We found that HF patients displayed a much lower increase in postprandial intact and total GLP-1 levels than controls. The increase in postprandial intact GLP-1 in HF patients correlated negatively with serum brain natriuretic peptide levels and DPP4 activity and positively with the glomerular filtration rate. Likewise, the postprandial increases in both intact and total GLP-1 were blunted in HF rats and were restored by DPP4 inhibition. Additionally, vehicle-treated HF rats displayed glucose intolerance and hyperinsulinemia, whereas normal glucose homeostasis was observed in vildagliptin-treated HF rats. We conclude that the postprandial increase in GLP-1 is blunted in non-diabetic HF. Impaired GLP-1 bioavailability after meal intake correlates with poor prognostic factors and may contribute to the establishment of a vicious cycle between glucose disturbance and HF development and progression.

Cardiovascular risk reduction with periodontal treatment in patients on the waiting list for renal transplantation.

BACKGROUND: Cardiovascular mortality is increased in chronic kidney disease, a condition with a high prevalence of periodontal disease. Whether periodontitis treatment improves prognosis is unknown. METHODS: The effect of periodontal treatment on the incidence of cardiovascular events and death in 206 waitlist hemodialysis subjects was compared with that in 203 historical controls who did not undergo treatment. Patients were followed up for 24 months or until death or transplantation. RESULTS: The prevalence of moderate/severe periodontitis was 74%. Coronary artery disease correlated with the severity of periodontal disease (P = .02). Survival free of cardiovascular events (94% vs 83%, log-rank 0.009), coronary events (97% vs 89%, log-rank = 0.009), and cardiovascular death (96% vs 87%, log-rank = 0.037) was higher in the evaluated group. Death by any cause did not differ between groups. Multivariate analysis showed that treatment was associated with reduction in cardiovascular events (HR 0.43; 95% CI 0.22-0.87), coronary events (HR 0.31; 95% CI 0.12-0.83), and cardiovascular deaths (HR 0.43; 95% CI 0.19-0.98). CONCLUSION: Periodontal treatment reduced the 24-month incidence of cardiovascular events and cardiovascular death, suggesting that periodontal treatment may improve cardiovascular outcomes. We suggest that periodontal screening and eventual treatment may be considered in patients with advanced renal disease.

Incremental prognostic value of kidney function decline over coronary artery disease for cardiovascular event prediction after coronary computed tomography.

It is unknown whether mild chronic kidney disease (CKD) is associated with adverse cardiovascular (CV) prognosis after accounting for coronary artery disease (CAD). Here we evaluated the interplay between CKD and CAD in predicting CV death or myocardial infarction (MI) and all-cause death. We included 1541 consecutive patients in the Partners registry (mean age 55 years, 43% female) over 18 years old with no known prior CAD who underwent coronary computed tomography angiography (CCTA). The results of CCTA were categorized as normal, nonobstructive (under half), or obstructive (half and over). Overall, 653 of the patients had no CAD, 583 had nonobstructive CAD, and 305 had obstructive CAD, while 1299 had eGFR over 60 ml/min per 1.73 m(2) and 242 had an eGFR under this value. The presence and severity of CAD was significantly associated with an increased rate of CV death or MI and all-cause death, even after adjustment for age, gender, symptoms, and risk factors. Similarly, reduced eGFR was significantly associated with CV death or MI and all-cause death after similar adjustment. The addition of reduced GFR to a model which included both clinical variables and CCTA findings resulted in significant improvement in the prediction of CV death or MI and all-cause death. Thus, among individuals referred for CCTA to evaluate CAD, renal dysfunction is associated with an increased rate of CV events, mainly driven by an increase in the rate of noncoronary CV events. In this group of patients, both eGFR and the presence and severity of CAD together improve the prediction of future CV events and death.

Coronary events in obese hemodialysis patients before and after renal transplantation.

We examined the impact of obesity (BMI ≥30 kg/m(2) , n = 357) on prognosis in 1696 hemodialysis (HD) patients before and after renal transplantation (TX). End-points were coronary events, composite cardiovascular (CV) events, and death. Obese HD patients were older (55.9 ± 9.2 vs. 54.2 ± 11), had more diabetes (54% vs. 40%), dyslipidemia (49% vs. 30%), altered myocardial scan (38% vs. 31%), myocardial infarction (MI) (16% vs. 10%), coronary intervention (11% vs. 7%), higher total cholesterol (186 ± 52 vs. 169 ± 47), and triglycerides (219 ± 167 vs. 144 ± 91). Obese undergoing TX had more dyslipidemia (46% vs. 31%), angina (23% vs. 14%), MI (18% vs. 5%), increased total cholesterol (185 ± 56 vs. 172 ± 48), and triglycerides (237 ± 190 vs. 149 ± 100). Obesity was independently associated with coronary events (log-rank = 0.008, HR 2.55% CI 1.27-5.11) and death (log-rank 0.046, HR 1.52, % CI 1.007-2.30) in TX but not in HD. Obese HD patients had more risk factors and ischemic heart disease, but these characteristics did not interfere with prognosis. In TX patients, obesity predicts coronary events and death.

Peripheral Artery Disease Diagnosed by Pulse Palpation as a Predictor of Coronary Artery Disease in Patients with Chronic Kidney Disease.

There is a need of simple, inexpensive, and reliable noninvasive testing to predict coronary artery disease (CAD) in patients with chronic kidney disease (CKD), where the prevalence of cardiovascular (CV) events and death is elevated. We analyzed the association between peripheral artery disease (PAD) and CAD in 201 patients with stage 5 CKD on dialysis using a prospective observational cohort. Diagnosis of PAD by both palpation and USD were significantly correlated. In patients with PAD diagnosed by palpation, CAD was observed in 80%, while in those diagnosed by USD, CAD was present in 79.1%. The absence of a pulse by palpation predicted CAD with a sensitivity of 55% and a specificity of 76%; USD showed a sensitivity of 62% and specificity of 60% to predict CAD. The risk of combined serious CV events and death was significantly higher in subjects with PAD diagnosed by palpation, but not by USD. PAD assessed by palpation also correlated with the occurrence of multivessel CAD and with the probability of coronary intervention. Both methods are moderately useful for predicting CAD, but PAD diagnosis by palpation was a better predictor of combined CV events and death and was also associated with CAD severity and likelihood of intervention.

Interdialytic Blood Pressure and Risk of Cardiovascular Events and Death in Hemodialysis Patients.

INTRODUCTION: Normal (120-140 mm Hg) systolic peridialysis blood pressure (BP) is associated with higher mortality in hemodialysis (HD) patients. AIM: We explored the relationship between hypertension and BP on outcomes using data collected at the interdialytic period. METHODS: This was a single-center observational cohort study with 2672 HD patients. BP was determined at inception, in mid-week, between 2 consecutive dialysis sessions. Hypertension was defined as systolic BP ≥ 140 mm Hg and/or diastolic BP ≥ 90 mm Hg. Endpoints were major CV events and all-cause mortality. RESULTS: During a median follow-up of 31 months, 761 patients (28%) experienced CV events and 1181 (44%) died. Hypertensive patients had lower survival free of CV than normotensive patients (P = 0.031). No difference occurred in the incidence of death between groups. Compared with the reference category of SBP ≥ 171 mmHg, the incidence of cardiovascular events was reduced in patients with SBP 101-110 (HR 0.647, 95% CI 0.455 to 0.920), 111-120 (HR 0.663, 95%CI 0.492 to 0.894), 121-130 (HR 0.747, 95%CI 0.569 to 0.981), and 131-140 (HR 0.757, 95%CI 0.596 to 0.962). On multivariate analysis, systolic and diastolic BP were not independent predictors of CV events or death. Normal interdialytic BP was not associated with mortality or CV events, and hypertension predicted an increased probability of CV complications. CONCLUSIONS: Interdialytic BP may be preferred to guide treatment decisions, and HD patients should be treated according to guidelines for the general population until specific BP targets for this population are identified.

Evolving Management Paradigm for Stable Ischemic Heart Disease Patients: JACC Review Topic of the Week.

Management of stable coronary artery disease (CAD) has been based on the assumption that flow-limiting atherosclerotic obstructions are the proximate cause of angina and myocardial ischemia in most patients and represent an important target for revascularization. However, the role of revascularization in reducing long-term cardiac events in these patients has been limited mainly to those with left main disease, 3-vessel disease with diabetes, or decreased ejection fraction. Mounting evidence indicates that nonepicardial coronary causes of angina and ischemia, including coronary microvascular dysfunction, vasospastic disorders, and derangements of myocardial metabolism, are more prevalent than flow-limiting stenoses, raising concerns that many important causes other than epicardial CAD are neither considered nor probed diagnostically. There is a need for a more inclusive management paradigm that uncouples the singular association between epicardial CAD and revascularization and better aligns diagnostic approaches that tailor treatment to the underlying mechanisms and precipitants of angina and ischemia in contemporary clinical practice.

The Role of Ivabradine in Managing Symptomatic Patients with Chronic Coronary Syndromes: A Clinically Oriented Approach.

Angina is a significant contributor to disability and impairment in quality of life in patients with chronic coronary syndromes (CCS). An elevated heart rate (HR) may trigger myocardial ischemia by increasing oxygen consumption and decreasing the diastolic time, compromising the coronary flow. HR-lowering strategies offer symptom control and prevent cardiovascular events in subgroups of patients with CCS. However, the best therapeutic approach to achieve the desired HR in patients with CCS can be challenging based on efficacy and tolerability. Guidelines usually propose ß-blockers and/or non-dihydropyridine calcium channel blockers (CCB) for angina patients with elevated HR. Nonetheless, there is no clear evidence of greater antianginal efficacy of this strategy versus an alternative HR-lowering agent. Ivabradine reduces the HR by blocking the If current in the sinoatrial node without affecting myocardial contractility or vascular tone. The magnitude of the HR reduction by ivabradine is proportional to the initial HR, which decreases the risk of significant bradycardia. Ivabradine increases the diastolic time and the coronary flow reserve to a greater extent than ß-blockers and favors collateralization, improving the regional blood flow. We present two clinical cases of patients with symptomatic CCS in whom HR control with ivabradine was fundamental for symptom control and improvement in left ventricular (LV) function. An earlier combination of ivabradine plus ß-blockers would have provided more rapid symptom control and improved LV function in the first case. In the second case, the primary mechanism responsible for angina was most likely a coronary vasomotor abnormality, in which the use of ß-blockers aggravated the discomfort. The combination of a dihydropyridine CCB plus ivabradine was highly influential in symptom control. Due to its effects beyond HR reduction and good tolerability, ivabradine should be considered an essential ally in managing patients with angina and high HR with or without LV dysfunction.

Invasive coronary artery disease assessment and myocardial infarction in patients on renal replacement therapy.

BACKGROUND: The incidence of myocardial infarction (MI) is elevated in patients receiving renal replacement therapy (RRT). We hypothesized that an invasive strategy of assessment of coronary artery disease (CAD) will identify patients more prone to developing MI. METHODS: This was a single-center observational cohort study that included 1678 patients receiving RRT (hemodialysis and renal transplantation) assessed for CAD prospectively and analyzed retrospectively. Endpoints were the incidence of MI and death. RESULTS: The median follow-up was 43 months, and 180 patients experienced an MI with a mortality rate of 74%. Multivariate analysis showed that diabetes (HR 1.633; 95% CI 1.165-2.289), prior MI (HR 1.724; 95% CI 1.153-2.579), and CAD (HR 2.073; 95% CI 1.400-3.071) were predictors of MI. Altered myocardial scan did not correlate with MI. At the discretion of the attending physicians, 20/180 patients (11%) underwent coronary intervention that was associated with a higher cumulative survival (Log-rank 0.007). CONCLUSION: Patients with CAD suffered an MI more frequently, independently of symptoms and risk factors for MI, including noninvasive testing. Because of the elevated rate of the lethality of MI, invasive coronary studies may be indicated in select patients on RRT. Once an MI occurs, our data suggest that an invasive therapeutic approach is warranted.

Unraveling the interplay between dipeptidyl peptidase 4 and the renin-angiotensin system in heart failure.

AIMS: Emerging evidence suggests the existence of a crosstalk between dipeptidyl peptidase 4 (DPP4) and the renin-angiotensin system (RAS). Therefore, combined inhibition of DPP4 and RAS may produce similar pharmacological effects rather than being additive. This study tested the hypothesis that combining an inhibitor of DPP4 with an angiotensin II (Ang II) receptor blocker does not provide additional cardioprotection compared to monotherapy in heart failure (HF) rats. MAIN METHODS: Male Wistar rats were subjected to left ventricle (LV) radiofrequency ablation or sham operation. Six weeks after surgery, radiofrequency-ablated rats who developed HF were assigned into four groups and received vehicle (water), vildagliptin, valsartan, or both drugs, for four weeks by oral gavage. KEY FINDINGS: Vildagliptin and valsartan in monotherapy reduced LV hypertrophy, alleviated cardiac interstitial fibrosis, and improved systolic and diastolic function in HF rats, with no additional effect of combination treatment. HF rats displayed higher cardiac and serum DPP4 activity and abundance than sham. Surprisingly, not only vildagliptin but also valsartan in monotherapy downregulated the catalytic function and expression levels of systemic and cardiac DPP4. Moreover, vildagliptin and valsartan alone or in combination comparably upregulate the components of the cardiac ACE2/Ang-(1-7)/MasR while downregulating the ACE/Ang II/AT1R axis. SIGNIFICANCE: Vildagliptin or valsartan alone is as effective as combined to treat cardiac dysfunction and remodeling in experimental HF. DPP4 inhibition downregulates classic RAS components, and pharmacological RAS blockade downregulates DPP4 in the heart and serum of HF rats. This interplay between DPP4 and RAS may affect HF progression and pharmacotherapy.

Diabetes, Cardiovascular Disease, and Cardiovascular Risk in Patients with Chronic Kidney Disease.

INTRODUCTION: It is unclear whether the increased risk associated with diabetes in patients on dialysis is due to diabetes or a consequence of associated cardiovascular disease (CVD). AIM: The purpose of this work was to answer the question: do diabetes and CVD have a similar impact on the incidence of cardiovascular events in patients undergoing maintenance hemodialysis? METHODS: A prespecified protocol was used to prospectively evaluate and follow up 310 diabetic patients on hemodialysis without clinical evidence of CVD and 395 nondiabetic patients with CVD. Endpoint was the incidence of composite CV events and coronary events. RESULTS: The incidence of composite CV events (log-rank = 0.540) and coronary events (log-rank = 0.400) did not differ between groups. Because of the potential influence of occult CVD in patients with diabetes, we repeated the analysis excluding subjects with altered ejection fraction, a myocardial perfusion scan defect, and coronary artery disease in the group of patients with diabetes. Again we found no difference between groups (log-rank = 0.657). CONCLUSION: In patients on hemodialysis, diabetes and CVD carry similar risks for CV events. These results are congruent with the diabetes mellitus-CVD equivalence risk concept reported in the general population.

Myocardial scintigraphy and clinical stratification as predictors of events in renal transplant candidates.

BACKGROUND: We tested the hypothesis that the universal application of myocardial scanning with single-photon emission computed tomography (SPECT) would result in better risk stratification in renal transplant candidates (RTC) compared with SPECT being restricted to patients who, in addition to renal disease, had other clinical risk factors. METHODS: RTCs (n=363) underwent SPECT and clinical risk stratification according to the American Society of Transplantation (AST) algorithm and were followed up until a major adverse cardiovascular event (MACE) or death. RESULTS: Of the 363 patients, 79 patients (22%) had an abnormal SPECT scan and 270 (74%) were classified as high risk. Both methods correctly identified patients with increased probability of MACE. However, clinical stratification performed better (sensitivity and negative predictive value 99% and 99% vs. 25% and 87%, respectively). High-risk patients with an abnormal SPECT scan had a modest increased risk of events (log-rank = 0.03; hazard ratio [HR] = 1.37; 95% confidence interval [95% CI], 1.02-1.82). Eighty-six patients underwent coronary angiography, and coronary artery disease (CAD) was found in 60%. High-risk patients with CAD had an increased incidence of events (log-rank = 0.008; HR=3.85; 95% CI, 1.46-13.22), but in those with an abnormal SPECT scan, the incidence of events was not influenced by CAD (log-rank = 0.23). Forty-six patients died. Clinical stratification, but not SPECT, correlated with the probability of death (log-rank = 0.02; HR=3.25; 95% CI, 1.31-10.82). CONCLUSION: SPECT should be restricted to high-risk patients. Moreover, in contrast to SPECT, the AST algorithm was also useful for predicting death by any cause in RTCs and for selecting patients for invasive coronary testing.

Cardiac MRI for detection of unrecognized myocardial infarction in patients with end-stage renal disease: comparison with ECG and scintigraphy.

OBJECTIVE: The purposes of this study were to use the myocardial delayed enhancement technique of cardiac MRI to investigate the frequency of unrecognized myocardial infarction (MI) in patients with end-stage renal disease, to compare the findings with those of ECG and SPECT, and to examine factors that may influence the utility of these methods in the detection of MI. SUBJECTS AND METHODS: We prospectively performed cardiac MRI, ECG, and SPECT to detect unrecognized MI in 72 patients with end-stage renal disease at high risk of coronary artery disease but without a clinical history of MI. RESULTS: Fifty-six patients (78%) were men (mean age, 56.2 +/- 9.4 years) and 16 (22%) were women (mean age, 55.8 +/- 11.4). The mean left ventricular mass index was 103.4 +/- 27.3 g/m(2), and the mean ejection fraction was 60.6% +/- 15.5%. Myocardial delayed enhancement imaging depicted unrecognized MI in 18 patients (25%). ECG findings were abnormal in five patients (7%), and SPECT findings were abnormal in 19 patients (26%). ECG findings were false-negative in 14 cases and false-positive in one case. The accuracy, sensitivity, and specificity of ECG were 79.2%, 22.2%, and 98.1% (p = 0.002). SPECT findings were false-negative in six cases and false-positive in seven cases. The accuracy, sensitivity, and specificity of SPECT were 81.9%, 66.7%, and 87.0% (not significant). During a period of 4.9-77.9 months, 19 cardiac deaths were documented, but no statistical significance was found in survival analysis. CONCLUSION: Cardiac MRI with myocardial delayed enhancement can depict unrecognized MI in patients with end-stage renal disease. ECG and SPECT had low sensitivity in detection of MI. Infarct size and left ventricular mass can influence the utility of these methods in the detection of MI.

Intramyocardial injection of autologous bone marrow cells as an adjunctive therapy to incomplete myocardial revascularization--safety issues.

OBJECTIVES: To determine the safety of intramyocardial injection of autologous bone marrow cells in patients undergoing surgical myocardial revascularization (CABG) for severe coronary artery disease. INTRODUCTION: There is little data available regarding the safety profile of autologous bone marrow cells injected during surgical myocardial revascularization. Potential risks include arrythmias, fibrosis in the injected sites and growth of non-cardiac tissues. METHODS: Ten patients (eight men) were enrolled; they were 59+/-5 years old with limiting angina and were non-optimal candidates for complete CABG. Bone marrow cells (1.3+/-0.3x10(8)) were obtained prior to surgery, and the lymphomonocytic fraction (CD34+ =1.8+/-0.3%) was separated by density gradient centrifugation. During surgery, bone marrow cells were injected in non-grafted areas of ischemic myocardium. During the first year after surgery, the patients underwent laboratory tests, cardiac imaging, and 24-hour ECG monitoring. RESULTS: Injected segments: inferior (n=7), anterior (n=2), septal (n=1), apical (n=1), and lateral (n=1) walls. Except for a transient elevation of C-reactive protein at one month post-surgery (P=0.01), laboratory tests results were within normal ranges; neither complex arrhythmias nor structural abnormalities were detected during follow-up. There was a reduction in functional class of angina from 3.6+/-0.8 (baseline) to 1.2+/-0.4 (one year) (P<0.0001). Also, patients had a significant decrease in the ischemic score assessed by magnetic resonance, not only globally from 0.65+/-0.14 (baseline) to 0.17+/-0.05 (one year) (P=0.002), but also in the injected areas from 1.11+/-0.20 (baseline) to 0.34+/-0.13 (one year) (P=0.0009). CONCLUSIONS: Intramyocardial injection of bone marrow cells combined with CABG appears to be safe. Theoretical concerns with arrhythmias and/or structural abnormalities after cell therapy were not confirmed in this safety trial.

Evaluation of a protocol for coronary artery disease investigation in asymptomatic elderly hemodialysis patients.

BACKGROUND: Coronary artery disease (CAD) is prevalent in older patients on dialysis, but the prognostic relevance of coronary assessment in asymptomatic subjects remains undefined. We tested the usefulness of a protocol, based on clinical, invasive, and noninvasive coronary assessment, by answering these questions: Could selecting asymptomatic patients for coronary invasive assessment identify those at higher risk of events? Is CAD associated with a worse prognosis? METHODS: A retrospective study including 276 asymptomatic patients at least 65 years old on the waiting list, prospectively evaluated for CAD and followed up until death or renal transplantation, were classified into two groups: 1) low-risk patients who did not undergo coronary angiography (n=63) and 2) patients who did undergo angiography (n=213). The latter group was reclassified into patients with significant CAD or normal angiograms/nonsignificant CAD. RESULTS: CAD (≥70% stenosis) occurred in 124 subjects (58%). The incidence of death by any cause, coronary death, and major cardiovascular (CV) events were similar in patients selected or not for angiography and in those with or without significant CAD. Myocardial revascularization (surgical/percutaneous) was performed in only 21/276 patients (7.6%) and did not result in a reduction in mortality. CONCLUSION: In older patients on renal replacement therapy, the prevalence of CAD was high, but coronary investigation was not useful as a risk stratification tool and also resulted in a rather small proportion of patients eligible for intervention. Therefore, in the elderly, coronary investigation should not be considered routine in asymptomatic patients.

Parathyroidectomy reduces cardiovascular events and mortality in renal hyperparathyroidism.

BACKGROUND: Secondary hyperparathyroidism (SHPT) and its associated abnormalities in mineral metabolism increase the risk of cardiovascular morbidity and death in chronic renal failure (CRF). The effect of parathyroidectomy (PTX) on the incidence of major cardiovascular events in CRF patients with SHPT is unknown. We tested the hypothesis that PTX reduces the incidence of cardiovascular complications and death in CRF patients with severe SHPT scheduled for PTX, comparing the outcome of patients treated or not treated by PTX. METHODS: The study comprised 118 CRF patients with SHPT on maintenance hemodialysis, unresponsive to medical treatment and scheduled for PTX. Patients underwent comprehensive cardiovascular evaluations at baseline. They were followed up until death, occurrence of major cardiovascular events, or kidney transplantation. RESULTS: No deaths related to PTX occurred. After a median follow-up of 30 months, 50 patients (42%) had undergone PTX whereas 68 (58%) had not. The groups were comparable in terms of age, sex, race, serum parathyroid hormone, calcium or phosphate, calcium x phosphate product, and all major cardiovascular variables, except diastolic blood pressure. PTX was associated with a reduced incidence of major cardiovascular events (P = .02) and overall mortality (P

Screening for significant coronary artery disease in high-risk renal transplant candidates.

BACKGROUND: Renal transplant candidates are at an increased risk for coronary artery disease (CAD), a strong predictor of cardiovascular events [major adverse coronary events (MACE)]. Coronary angiography is a costly, risky, invasive procedure. We sought to determine clinical predictors of significant CAD (stenosis > or =70%) in high-risk renal transplant candidates. METHODS: Clinical evaluation and coronary angiography were performed in 301 patients (57+/-8 years, 73% men) on hemodialysis for 32 months (median). Patients were followed-up for 22 months (median). Inclusion criteria were diabetes (type 1 or 2), evidence of cardiovascular disease, or age > or =50 years. Risk factors included hypertension (93.7%), overweight/obesity (54.3%), dyslipidemia (44.9%), diabetes (42.1%), and smoking (24.3%). Cardiovascular disease was found as follows: peripheral arterial disease (PAD) (31.2%), angina (28.1%), stroke (12.9%), myocardial infarction (MI) (10.3%), and heart failure (9.3%). RESULTS: Significant CAD was found in 136 individuals (45.2%). Diabetes [odds ratio (OR)=1.82; 95% confidence interval (CI)=1.08-3.07], PAD (OR=2.50; 95% CI=1.44-4.37), and previous MI (OR=7.75; 95% CI=3.03-23.98) were associated with significant CAD. The prevalence of significant CAD increased with the number of clinical predictors from 26% (none) to 100% (all present) (P<0.0001). The incidence of fatal/nonfatal MACE increased two, four, and sixfold in those with diabetes, PAD, or previous MI, respectively (P<0.0001). CONCLUSIONS: In high-risk patients with end-stage renal disease, the prevalence of CAD and the incidence of MACE were high. Significant CAD or cardiovascular complications were not related to the majority of classic risk factors. Patients with diabetes, PAD, or previous MI are at higher risk of CAD, MACE, or both and, thus, must be referred for invasive diagnostic procedures.